Tumorigenicity of 7,12-dimethylbenz[a]anthracene, its hydroxymethylated derivatives and selected dihydrodiols in the newborn mouse.
The newborn mouse lung adenoma model has been shown to be a sensitive test for studying the tumorigenicity of bay region diol epoxides and their precursor dihydrodiols. When a total dose of 28 nmol of 7,12-dimethylbenz[a]anthracene (DMBA) or its derivatives was injected i.p. into the preweaning mice, it was found that the 3,4-dihydrodiols of both DMBA and 7-hydroxymethyl-12-methylbenz[a]anthracene caused 13.3 and 4.1 times more lung adenomas than DMBA, respectively. The mice treated with the 5,6- and 8,9-dihydrodiols of DMBA, 7-hydroxymethyl-12-methylbenz[a]anthracene and its 5,6- and 8,9- and 10,11-dihydrodiols, 7-methyl-12-hydroxymethylbenz[a]anthracene and 7,12-dihydroxymethylbenz[a]anthracene developed a level of lung adenomas/mouse less than 2-fold higher than that found in the DMSO-treated control group. Liver tumors also developed in some of the mice. The percentage of mice with liver tumors also indicated that the 3,4-dihydrodiols of both DMBA and 7-hydroxymethyl-12-methylbenz[a]anthracene were more tumorigenic than DMBA itself. These data indicate that the 3,4-dihydrodiols of both DMBA and its 7-hydroxymethyl derivative may be proximate carcinogenic metabolites of DMBA in the newborn mouse.
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000633:toxicity*; D000236:Adenoma / Q000139:chemically induced; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001551:Benz(a)Anthracenes / Q000633:toxicity*; D002273:Carcinogens; D005260:Female; D006900:Hydroxylation; D008113:Liver Neoplasms / Q000139:chemically induced; D008175:Lung Neoplasms / Q000139:chemically induced; D008745:Methylation; D051379:Mice; D011247:Pregnancy
D001551:Benz(a)Anthracenes; D002273:Carcinogens; D015127:9,10-Dimethyl-1,2-benzanthracene